Prognostic markers of ferroptosis-related long non-coding RNA in lung adenocarcinomas

Abstract

Ferroptosis is a recently established type of iron-dependent programmed cell death. Growing studies have focused on the function of ferroptosis in cancers, including lung adenocarcinoma (LUAD). However, the factors involved in the regulation of ferroptosis-related genes are not fully understood. In this study, we collected data from lung adenocarcinoma datasets of the Cancer Genome Atlas (TCGA-LUAD). The expression profiles of 60 ferroptosis-related genes were screened, and two differentially expressed ferroptosis subtypes were identified. We found the two ferroptosis subtypes can predict clinical outcomes and therapeutic responses in LUAD patients. Furthermore, key long non-coding RNAs (lncRNAs) were screened by single factor Cox and least absolute shrinkage and selection operator (LASSO) based on which co-expressed with the 60 ferroptosis-related genes. We then established a risk score model which included 13 LUAD ferroptosis-related lncRNAs with a multi-factor Cox regression. The risk score model showed a good performance in evaluating the outcome of LUAD. What’s more, we divided TCGA-LUAD tumor samples into two groups with high- and low-risk scores and further explored the differences in clinical characteristics, tumor mutation burden, and tumor immune cell infiltration among different LUAD tumor risk score groups and evaluate the predictive ability of risk score for immunotherapy benefit. Our findings provide good support for immunotherapy in LUAD in the future.

FKBP3, a poor prognostic indicator, promotes the progression of LUAD via regulating ferroptosis and immune infiltration

“…[21] Although ferroptosis was considered as the effective potential to overcome cancer progression, till now, the exact mechanism of ferroptosis in LUAD progression remains elusive. [22,23] In the present study, we downloaded the RNAseq data and clinical data of human LUAD from TCGA and Wilcoxon rank sum test was performed to selected the prognosis-related DEGs in LUAD patients. We also downloaded the ferroptosis-related datasets from GeneCards and the intersecting genes were selected, including ALG3, H2AX, VDAC1, RUVBL2, FKBP3, CISD2, TFAP2A and LDHA, all of which were involved in the ferroptosis of cancer cells.…”

Iron Chelation as a Potential Therapeutic Approach in Acute Lung Injury

“…For example, it is reported that LPS-stimulated mouse alveolar macrophages increased the expression of hepcidin mRNA and decreased transmembrane protein ferroportin (FPN) mRNA, leading to a reduction in iron efflux, and the results suggest that the lung hepcidin–FPN axis may correlate with iron homeostasis during alveolar macrophage injury induced by LPS [ 9 ]. Recently, long non-coding RNAs (lncRNAs) have been considered as important mediators of iron metabolism [ 10 ]. Through regulating the amount and function of iron, seven iron metabolism–related lncRNAs are recognized as an independent prognostic factor for the overall survival of lung adenocarcinoma patients.…”